Diagnosis of disease and determination of treatment efficacy are important tools in medicine. In particular, detection of IgE production in an animal can be indicative of disease. Such diseases include, for example, allergy, atopic disease, hyper IgE syndrome, internal parasite infections and B cell neoplasia. In addition, detection of IgE production in an animal following a treatment is indicative of the efficacy of the treatment, such as when using treatments intended to disrupt IgE production.
Until the discovery of the present invention, detection of IgE in samples obtained from non-human animals has been hindered by the absence of suitable reagents for detection of IgE. Various compounds have been used to detect IgE in IgE-containing compositions. In particular, antibodies that bind selectively to epsilon idiotype antibodies (i.e., anti-IgE antibodies) have been used to detect IgE. These anti-IgE antibodies, however, can cross-react with other antibody idiotypes, such as gamma isotype antibodies. The discovery of the present invention includes the use of a Fc epsilon receptor (FcεR) molecule to detect the presence of IgE in a putative IgE-containing composition. A FcεR molecule provides an advantage over, for example anti-IgE antibodies, to detect IgE because a FcεR molecule can bind to an IgE with more specificity (i.e., less idiotype cross-reactivity) and more sensitivity (i.e., affinity) than anti-IgE binding antibodies.
Lowenthal et al., 1993, Annals of Allergy 71:481–484, dog serum can transfer cutaneous reactivity to a human. While it is possible that Lowenthal et al. properly teach the binding of human FcεR to canine IgE. Lowenthal et al., however, do not provide data defining the particular cellular proteins responsible for the transfer of cutaneous reactivity. As such, a skilled artisan would conclude that the transfer of cutaneous reactivity taught by Lowenthal et al. could be due to a variety of different molecular interactions and that the conclusion drawn by Lowenthal et al. is merely an interpretation. In addition, Lowenthal et al. do not teach the use of purified human FcεR to detect canine IgE. The subunits of human FcεR have been known as early as 1988 and have never been used to detect canine, feline or equine IgE. Indeed, U.S. Pat. No. 4,962,035, to Leder et al., issued Oct. 9, 1990, discloses human FcεR but does not disclose the use of such a human FcεR to detect human or non-human IgE. The use of purified human FcεR avoids complications presented by use of FcεR bound to a cell, such as non-specific binding of the FcεR-bearing cell due to additional molecules present on the cell membrane. That purified human FcεR detects non-human IgE is unexpected because inter-species binding between a FcεR and an IgE is not predictable. For example, human FcεR binds to rat IgE but rat FcεR does not bind to human IgE.
The high affinity FcεR consists of three protein chains, alpha, beta and gamma. Prior investigators have disclosed the nucleic acid sequence for: the alpha chain (Kochan et al., Nucleic Acids Res. 16:3584, 1988; Shimizu et al., Proc. Natl. Acad. Sci. USA 85:1907–1911, 1988; and Pang et al., J. Immunol. 151:6166–6174, 1993); the beta chain (Kuster et al., J. Biol. Chem. 267:12782–12787, 1992); and the gamma chain (Kuster et al., J. Biol. Chem. 265:6448–6452, 1990).
Thus, methods and kits are needed in the art that will provide specific detection of non-human IgE.